scholarly journals Disulfide bond disrupting agents activate the unfolded protein response in EGFR- and HER2-positive breast tumor cells

Oncotarget ◽  
2017 ◽  
Vol 8 (17) ◽  
pp. 28971-28989 ◽  
Author(s):  
Renan B. Ferreira ◽  
Mengxiong Wang ◽  
Mary E. Law ◽  
Bradley J. Davis ◽  
Ashton N. Bartley ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Tumor Cells ◽  
Disulfide Bond ◽  
Breast Tumor ◽  
Her2 Positive ◽  
Breast Tumor Cells ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Abstract 2081: The unfolded protein response relieves stress in tumor cells by stimulating angiogenesis

2011 ◽  
Author(s):  
Yugang Wang ◽  
Yu Ning ◽  
Goleeta Alam ◽  
Fernanda Visioli ◽  
Jacques E. Nör ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Tumor Cells ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals USP22 promotes HER2-driven mammary carcinoma aggressiveness by suppressing the unfolded protein response

Oncogene ◽  
2021 ◽  
Author(s):  
Evangelos Prokakis ◽  
Anna Dyas ◽  
Regina Grün ◽  
Sonja Fritzsche ◽  
Upasana Bedi ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Tumor Cells ◽  
Extended Period ◽  
Unfolded Protein ◽  
Promote Cell Survival ◽  
Specific Protease ◽  
Underlying Mechanisms ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractThe Ubiquitin-Specific Protease 22 (USP22) is a deubiquitinating subunit of the mammalian SAGA transcriptional co-activating complex. USP22 was identified as a member of the so-called “death-from-cancer” signature predicting therapy failure in cancer patients. However, the importance and functional role of USP22 in different types and subtypes of cancer remain largely unknown. In the present study, we leveraged human cell lines and genetic mouse models to investigate the role of USP22 in HER2-driven breast cancer (HER2+-BC) and demonstrate for the first time that USP22 is required for the tumorigenic properties in murine and human HER2+-BC models. To get insight into the underlying mechanisms, we performed transcriptome-wide gene expression analyses and identified the Unfolded Protein Response (UPR) as a pathway deregulated upon USP22 loss. The UPR is normally induced upon extrinsic or intrinsic stresses that can promote cell survival and recovery if shortly activated or programmed cell death if activated for an extended period. Strikingly, we found that USP22 actively suppresses UPR induction in HER2+-BC cells by stabilizing the major endoplasmic reticulum (ER) chaperone HSPA5. Consistently, loss of USP22 renders tumor cells more sensitive to apoptosis and significantly increases the efficiency of therapies targeting the ER folding capacity. Together, our data suggest that therapeutic strategies targeting USP22 activity may sensitize tumor cells to UPR induction and could provide a novel, effective approach to treat HER2+-BC.

scholarly journals The Unfolded Protein Response Induces the Angiogenic Switch in Human Tumor Cells through the PERK/ATF4 Pathway

2012 ◽  
Vol 72 (20) ◽  
pp. 5396-5406 ◽  
Author(s):  
Yugang Wang ◽  
Goleeta N. Alam ◽  
Yu Ning ◽  
Fernanda Visioli ◽  
Zhihong Dong ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Tumor Cells ◽  
Human Tumor ◽  
Human Tumor Cells ◽  
Angiogenic Switch ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5

2010 ◽  
Vol 120 (1) ◽  
pp. 127-141 ◽  
Author(s):  
Kasper M.A. Rouschop ◽  
Twan van den Beucken ◽  
Ludwig Dubois ◽  
Hanneke Niessen ◽  
Johan Bussink ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Tumor Cells ◽  
Human Tumor ◽  
Human Tumor Cells ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Misfolding of Collagen X Chains Harboring Schmid Metaphyseal Chondrodysplasia Mutations Results in Aberrant Disulfide Bond Formation, Intracellular Retention, and Activation of the Unfolded Protein Response

2005 ◽  
Vol 280 (16) ◽  
pp. 15544-15552 ◽  
Author(s):  
Richard Wilson ◽  
Susanna Freddi ◽  
Danny Chan ◽  
Kathryn S. E. Cheah ◽  
John F. Bateman
Keyword(s):  
Unfolded Protein Response ◽  
Growth Plate ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Unfolded Protein ◽  
Trimer Formation ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Nc1 Domain

Collagen X is a short chain collagen expressed specifically by the hypertrophic chondrocytes of the cartilage growth plate during endochondral bone formation. Accordingly,COL10A1mutations disrupt growth plate function and cause Schmid metaphyseal chondrodysplasia (SMCD). SMCD mutations are almost exclusively located in the NC1 domain, which is crucial for both trimer formation and extracellular assembly. Several mutations are expected to reduce the level of functional collagen X due to NC1 domain misfolding or exclusion from stable trimer formation. However, other mutations may be tolerated within the structure of the assembled NC1 trimer, allowing mutant chains to exert a dominant-negative impact within the extracellular matrix. To address this, we engineered SMCD mutations that are predicted either to prohibit subunit folding and assembly (NC1del10 and Y598D, respectively) or to allow trimerization (N617K and G618V) and transfected these constructs into 293-EBNA and SaOS-2 cells. Although expected to form stable trimers, G618V and N617K chains (like Y598D and NC1del10 chains) were secreted very poorly compared with wild-type collagen X. Interestingly, all mutations resulted in formation of an unusual SDS-stable dimer, which dissociated upon reduction. As the NC1 domain sulfhydryl group is not solvent-exposed in the correctly folded NC1 monomer, disulfide bond formation would result only from a dramatic conformational change. In cells expressing mutant collagen X, we detected significantly increased amounts of the spliced form of X-box DNA-binding protein mRNA and up-regulation of BiP, two key markers for the unfolded protein response. Our data provide the first clear evidence for misfolding of SMCD collagen X mutants, and we propose that solvent exposure of the NC1 thiol may trigger the recognition and degradation of mutant collagen X chains.

scholarly journals Role of the unfolded protein response in determining the fate of tumor cells and the promise of multi-targeted therapies

2017 ◽  
Vol 23 (3) ◽  
pp. 317-334 ◽  
Author(s):  
Kunyu Shen ◽  
David W. Johnson ◽  
David A. Vesey ◽  
Michael A. McGuckin ◽  
Glenda C. Gobe
Keyword(s):  
Unfolded Protein Response ◽  
Tumor Cells ◽  
Targeted Therapies ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response
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